Purpose: No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results.
Materials and methods: 134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant.
Results: Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140-159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02). Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69 patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68% compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two-year posttreatment biopsies were negative in 70% (33 of 47) of patients with a D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage revealed that dose was the most significant predictor of biochemical failure (p = 0.001). This dose response was more pronounced in patients presenting with PSA levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29).
Conclusion: A dose response was observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of 140-160 Gy using TG43 guidelines.